Edoxaban Treatment Versus Vitamin K Antagonist (VKA) in Patients With Atrial Fibrillation (AF) Undergoing Catheter Ablation (ELIMINATE-AF)

August 26, 2019 updated by: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

A Prospective, Randomized, Open-Label, Blinded Endpoint Evaluation (PROBE) Parallel Group Study Comparing Edoxaban vs. VKA in Subjects Undergoing Catheter Ablation of Non-valvular Atrial Fibrillation (ELIMINATE-AF)

There are insufficient data on the safety and efficacy of edoxaban therapy in subjects with AF following catheter ablation. This phase 3b study is designed to evaluate the safety and to explore the efficacy of an edoxaban-based antithrombotic regimen versus a VKA-based antithrombotic regimen in subjects with AF following catheter ablation. Bleeding is a central safety outcome in cardiovascular clinical trials, especially for antithrombotic strategies and invasive procedures.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

632

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerpen, Belgium, 2020
        • ZNA Middelheim
      • Brussels, Belgium, 1090
        • UZ Brussel
      • Brussels, Belgium, 1070
        • Erasme Hospital
      • Edegem, Belgium, 2650
        • Universitair Ziekenhuis Antwerpen
  • Canada
      • Calgary, Canada, T2N 4Z6
        • University of Calgary
      • Hamilton, Canada, L8L 2X2
        • Hamilton Health Sciences/McMaster University
      • Montréal, Canada, H1T 1C8
        • Montreal Heart Institute
      • Sherbrooke, Canada, J1H 5N4
        • Centre Hospitalier Universitaire de Sherbrooke
  • Czechia
      • Brno, Czechia, 625 00
        • FN BRNO
      • Brno, Czechia, 69691
        • St. Anne's University Hospital Brno, International Clinical Research Center
      • Prague, Czechia, 14021
        • IKEM
      • Prague, Czechia, 150 06
        • University Hospital Motol - Cardiology
      • Praha, Czechia, 100 34
        • FN Kralovske Vinohrady
      • Praha, Czechia, 128 08
        • VFN v Praze II. Interní klinika - Kardiologie a angiologie
      • Ústí nad Labem, Czechia, 40113
        • Masarykova nemocnice - Kardiologie Krajská zdravotní, a.s.
  • Germany
      • Bad Krozingen, Germany, 79189
        • Universitäts Herzzentrum Freiburg-Bad Krozingen Klinik für Kardiologie und Angiologie II
      • Berlin, Germany, 13353
        • Charité Universitätsmedizin Berlin - CVK Medizinische Klinik m.S. Kardiologie
      • Bielefeld, Germany, 33604
        • Klinikum Bielefeld Klinik für Kardiologie/internist. Intensivmedizin
      • Coburg, Germany, 96450
        • Klinikum Coburg GmbH II.Med.Klinik
      • Dortmund, Germany, 44137
        • Klinik für Innere Medizin I
      • Duesseldorf, Germany, 40225
        • University Clinic Duesseldorf Clinic for Cardiology, Pneumology and Angiology
      • Hamburg, Germany, 20251
        • Universitäres Herzzentrum Hamburg Kardiologie mit Schwerpunkt Elektrophysiologie
      • Heidelberg, Germany, 69120
        • University Hospital of Heidelberg Clinic of Cardiology, Angiology and Pneumology
      • Leipzig, Germany, 04289
        • Herzzentrum Leipzig - Universitätsklinik Abteilung für Rhythmologie
      • Muenster, Germany, 48149
        • Univ. of Muenster.Cardiovascular Medicine
      • Rostock, Germany, 18057
        • Universitätsmedizin Rostock Zentrum für Innere Medizin I, Kardiologie
      • Tübingen, Germany, 72076
        • Deutsches Herzk. Universitätsklinikum Tübingen Medizinische Klinik III. Kardiologie
      • Ulm, Germany, 89081
        • Universitätsklinikum Ulm
      • Wuerzburg, Germany, 97080
        • Universitätsklinikum Würzburg Medizinische Klinik und Poliklinik I
  • Hungary
      • Budapest, Hungary, 1122
        • Semmelweis Egyetem Varosmajori Sziv- es Ergyogyaszati Klinika
      • Budapest, Hungary, 1134
        • Magyar Honvédség Egészségügyi Központ Kardiológiai Osztály
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Kardiológiai és Szívsebészeti Klinika
      • Pécs, Hungary, H 7624
        • Pecs University Clinical Center
      • Szeged, Hungary, 6725
        • Szegedi Tudományegyetem II. Belgyógyászati Klnika és Kardiológiai Központ
      • Zalaegerszeg, Hungary, 8900
        • Zala Megyei Szent Rafael Kórház Kardiológia Osztály
  • Italy
      • Arezzo, Italy, 52100
        • Ospedale San Donato
      • Castel Volturno, Italy, 81030
        • Pineta Grande Hospital
      • Catanzaro, Italy, 88100
        • Universita' degli Studi Catanzaro
      • Cona, Italy, 44124
        • Arcispedale Sant'Anna
      • Firenze, Italy, 50122
        • Azienda USL Toscana
      • Grosseto, Italy, 58100
        • Ospedale della Misericordia
      • Mestre, Italy, 30174
        • Ospedale dell'Angelo
      • Monza, Italy, 80082
        • ASST Vimercate
      • Negrar, Italy, 37024
        • Ospedale Santo Cuore
      • Pavia, Italy, 27100
        • Istituto di Cura cittè di Pavia
      • Piacenza, Italy, 29124
        • Azienda Ospedaliera di Piacenza "Ospedale Guglielmo d Saliceto"
      • Roma, Italy, 00169
        • Policlinico Casilino
      • Rome, Italy, 00168
        • Largo Agostino Gemelli
      • Sant'Eramo, Italy, 70021
        • Ospedale Ecclesiastico "Miulli"
  • Korea, Republic of
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center
    • Gangnam-gu
      • Seoul, Gangnam-gu, Korea, Republic of, 06351
        • Samsung Medical Center
    • Jongno-gu
      • Seoul, Jongno-gu, Korea, Republic of, 03080
        • Seoul National University Hospital
    • Seodaemun-Gu
      • Seoul, Seodaemun-Gu, Korea, Republic of, 03722
        • Yonsei University Severance Hospital
    • Seoungbuk-gu
      • Seoul, Seoungbuk-gu, Korea, Republic of, 02841
        • Korea University Anam Hospital
  • Poland
      • Kraków, Poland, 31-501
        • University Hospital - Szpital Uniwersytecki
      • Lublin, Poland, 20-954
        • Samodzielny Publiczny Szpital Kliniczny Nr 4 Klinika Kardiologii
      • Warszawa, Poland, 04-073
        • Oddzial Kardiologii Szpital Grochowski im. dr R. Masztaka SPZOZ
      • Zabrze, Poland, 41-800
        • Oddział Kliniczny Kardiologii SUM Katedra Kardiologii
      • Łódź, Poland, 92-213
        • Klinika Intensywnej Terapii Kardiologicznej
  • Spain
      • Alicante, Spain, 03540
        • Hospital General Universitario
      • Barcelona, Spain, 08003
        • Hospital del Mar
      • Barcelona, Spain, 8036
        • Hospital Clinic Cardiologia
      • Madrid, Spain, 28040
        • Fundación Jiménez Díaz
      • San Juan de Alicante, Spain, 03550
        • Hospital Universitario San Juan de Alicante
  • Taiwan
      • Kaohsiung City, Taiwan, 83301
        • Chang Gung Memorial Hospital
      • Taichung City, Taiwan, 40447
        • China Medical University Hospital
      • Taichung City, Taiwan, 40705
        • Taichung Veterans General Hospital (VGH-TC)
      • Taipei, Taiwan, 112
        • Taipei Veterans General Hospital
      • Taoyuan City, Taiwan, 33305
        • Chang Gung Memorial Hospital
  • United Kingdom
      • Blackpool, United Kingdom, FY3 8NR
        • Blackpool Teaching Hospitals NHS
      • Bournemouth, United Kingdom, BH7 7DW
        • Royal Bournemouth Hospital
      • Cambridge, United Kingdom, CB23 3RE
        • Papworth Hospital NHS Trust
      • Leeds, United Kingdom, LS1 3EX
        • Leeds General Infirmary
      • London, United Kingdom, SE5 9RS
        • King's College Hospital
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham City Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female at least 18 years of age with documented history of paroxysmal (lasting ≤7 days), persistent (lasting >7 days but ≤12 months) or long-standing [long-lasting] persistent (>12 months) non-valvular AF. Duration of AF can be confirmed by any electrical tracing or a recording in the subject's medical records (e.g., medical chart, hospital discharge summary).
  • Subject is eligible and is scheduled for either radio frequency (RF) or cryoballoon catheter ablation (both first and repeated procedure included).
  • Signed informed consent form (ICF).

Exclusion Criteria:

  • AF considered to be of a transient or reversible nature (such as in myocarditis, post-surgery, ionic disturbances, thyrotoxicosis, pneumonia, severe anemia etc.).
  • Subject post stroke, or with a systemic thromboembolic event within the past 6 months prior to randomization.
  • Subject has a thrombus in the left atrial appendage (LAA), left atrium (LA), left ventricle (LV), or aorta, or an intracardial mass.
  • Subject had a myocardial infarction (MI) within the 2 months prior to randomization or coronary artery bypass graft (CABG) surgery within 3 months prior to the randomization.
  • Subject has signs of bleeding, history of clinically-relevant bleeding according to International Society on Thrombosis and Hemostasis (ISTH), or conditions associated with high risk of bleeding
  • Subjects with any contraindication for anticoagulant agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Edoxaban-based regimen
Edoxaban-based regimen for 21 days pre- and 90 days post-ablation period.
Drug: Edoxaban
Edoxaban 60 mg once-daily or 30 mg once-daily in selected subjects.
Other Names:
  • Lixiana
Active Comparator: VKA-based regimen
VKA-based regimen for 21 days pre- and 90 days post-ablation period (control regimen)
Drug: VKA-Based Regimen
Dosed at International Normalised Ratio (INR) levels, which is a test of how long it takes for blood to clot. Standard of Care treatment in Canada, Italy, Poland, Hungary, Czech Republic, United Kingdom (UK), Taiwan and Korea.
Other Names:
  • Warfarin
Drug: VKA-Based Regimen
Dosed at INR levels. Standard of Care treatment in Germany, Belgium, and the Netherlands.
Other Names:
  • Phenprogamma
  • Phenprocoumon
Drug: VKA-Based Regimen
Dosed at INR levels. Standard of Care treatment in France.
Other Names:
  • Previscan
  • Fluindione
Drug: VKA-Based Regimen
Dosed at INR levels. Standard of Care treatment in Spain.
Other Names:
  • Sintrom
  • Acenocoumarol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced the Composite of All-cause Death, Stroke (VARC-2), and Major Bleeding (ISTH) in the Edoxaban Group Compared With Vitamin K Antagonist (VKA) Group in Participants Undergoing Catheter Ablation (Adjudicated Data)
Time Frame: Day 1 to Day 90

Stroke (ischemic, hemorrhagic, or undetermined) was defined by Valve Academic Research Consortium-2 (VARC-2) as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury following hemorrhage or infarction. A stroke event was based on any of the following: duration of neurological dysfunction >24 hours (h), duration of neurological dysfunction <24 h in case of imaging-documented new hemorrhage or infarction, and a neurological dysfunction resulting in death.

Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability.
Day 1 to Day 90
Number of Participants Who Experienced Major Bleeding (International Society on Thrombosis and Hemostasis [ISTH]) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
Time Frame: Day 1 to Day 90
Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability.
Day 1 to Day 90

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Who Experienced the Composite of All-cause Death, Stroke (Alternative), and Major Bleeding (ISTH) in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
Time Frame: Day 1 to Day 90

An alternative definition characterized stroke (ischemic, hemorrhagic, or undetermined) as an abrupt onset, over minutes to hours, of a focal neurological deficit in the distribution of a single brain artery that was not due to an identifiable nonvascular cause (ie, brain tumor or trauma), and that either lasted at least 24 hours or resulted in death within 24 hours of onset.

Major bleeding was defined by the International Society on Thrombosis and Hemostasis (ISTH) as fatal bleeding and/or bleeding that is symptomatic and occurs in a critical area or organ and/or extrasurgical site bleeding causing a fall in hemoglobin level of >2 g/dL or leads to blood transfusion, surgical site bleeding that requires a second intervention, causes hemarthrosis that delays mobilization or wound healing, or causes hemodynamic instability.
Day 1 to Day 90
Number of Participants Who Experienced the Composite of Stroke (VARC-2), Systemic Embolic Events (SEE), and Cardiovascular (CV) Mortality in the Edoxaban Group Compared With VKA Group Among Participants Undergoing Catheter Ablation (Adjudicated Data)
Time Frame: Day 1 to Day 90

Stroke (ischemic, hemorrhagic, or undetermined) was defined by Valve Academic Research Consortium-2 (VARC-2) as an acute episode of focal or global neurological dysfunction caused by brain, spinal cord, or retinal vascular injury following hemorrhage or infarction. A stroke event was based on any of the following: duration of neurological dysfunction >24 hours (h), duration of neurological dysfunction <24 h in case of imaging-documented new hemorrhage or infarction, and a neurological dysfunction resulting in death.

SEE was defined as an arterial embolism resulting in clinical ischemia, excluding the central nervous system, coronary, and pulmonary arterial circulation.

CV mortality was defined as cardiac or vascular death according to Academic Research Consortium.
Day 1 to Day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2017

Primary Completion (Actual)

September 24, 2018

Study Completion (Actual)

September 24, 2018

Study Registration Dates

First Submitted

October 21, 2016

First Submitted That Met QC Criteria

October 21, 2016

First Posted (Estimate)

October 24, 2016

Study Record Updates

Last Update Posted (Actual)

September 23, 2019

Last Update Submitted That Met QC Criteria

August 26, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DSE-EDO-01-16-EU
  • 2016-003069-25 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/

IPD Sharing Time Frame

Studies for which the medicine and indication have received European Union (EU), US and/or Japan marketing approval on or after 01 January 2014 or by the US or EU Health Authorities when regulatory submissions in both regions are not planned and after the primary study results have been accepted for publication.

IPD Sharing Access Criteria

Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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